title: Simultaneous determination of antidementia drugs in human plasma for therapeutic drug monitoring.
abstract: BACKGROUND
  A simple liquid chromatography mass spectrometry method was developed and validated for the simultaneous determination of antidementia drugs, including donepezil, galantamine, rivastigmine and its major metabolite, NAP 226-90, and memantine.
  
  
  METHODS
  A solid phase extraction procedure with a mixed-mode sorbent was used to isolate the drugs from 0.5 mL human plasma. Reverse phase chromatographic separation of the compounds was obtained with a gradient elution of an ammonium acetate buffer at pH 9.3 and acetonitrile and the analytes were detected by mass spectrometry in the single ion monitoring mode.
  
  
  RESULTS
  The method was validated according to the recommendations of the Food and Drug Administration, including assessment of trueness (-8.0% to +10.7%), imprecision (repeatability: 1.1-4.9%, intermediate imprecision: 2.1-8.5%), selectivity and matrix effects variability (less than 6%) as well as short- and long-term stability in plasma. The calibration ranges were from 1 ng/mL to 300 ng/mL (rivastigmine and memantine) and 2 ng/mL to 300 ng/mL (donepezil, galantamine, and NAP 226-90).
  
  
  CONCLUSIONS
  The method was successfully applied to patients' samples and might contribute to evaluate whether a therapeutic drug monitoring-guided dose adjustment of antidementia drugs could contribute to minimize the risk of adverse reactions and to increase the probability of efficient therapeutic response.
authors.affiliation: Unit of Biochemistry and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, University of Lausanne, Hospital of Cery, Prilly, Switzerland .
authors.forename: Muriel
authors.initials: M
authors.lastname: Noetzli
authors.forename: Eva
authors.initials: E
authors.lastname: Choong
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ansermot
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D002800:Cholinesterase Inhibitors / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D002853:Chromatography, Liquid; D003704:Dementia / Q000188:drug therapy*; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D004359:Drug Therapy, Combination; D006801:Humans; D013058:Mass Spectrometry; D016202:N-Methylaspartate / Q000378:metabolism; D011619:Psychotropic Drugs / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
chemical_list: D002800:Cholinesterase Inhibitors; D011619:Psychotropic Drugs; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate